# Serum Cocaine- and Amphetamine-Regulated Transcript (CART) Levels in Graves’ Disease: Associations with Metabolic Status, Autoimmunity, and Thyroid Ultrasound Heterogeneity

## TL;DR

This study explores serum levels of a neuropeptide called CART in patients with Graves’ disease and finds associations with metabolic and autoimmune factors, but not with thyroid hormone levels.

## Contribution

The study identifies novel associations between serum CART levels and thyroid ultrasound heterogeneity, metabolic status, and autoimmunity in Graves’ disease.

## Key findings

- Serum CART levels were not significantly different between Graves’ disease patients and healthy controls.
- CART levels correlated with body mass index and insulin resistance but inversely with autoantibody levels in Graves’ disease patients.
- CART levels varied with thyroid ultrasound heterogeneity, suggesting a role in reflecting metabolic and autoimmune heterogeneity.

## Abstract

Graves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism and a hypermetabolic state involving complex endocrine, metabolic, and immune interactions. Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide involved in energy balance, neuroendocrine signaling, and neuroimmune modulation; however, its circulating levels and clinical relevance in GD remain unclear. In this single-center prospective study, serum CART levels were evaluated in 44 patients with GD and 44 age- and sex-matched healthy controls. Associations with thyroid function, autoimmune markers, metabolic parameters, and thyroid ultrasound heterogeneity were analyzed. Serum CART concentrations were measured using an enzyme-linked immunosorbent assay, and clinical, biochemical, and ultrasonographic data were recorded. Serum CART levels did not differ significantly between GD patients and healthy controls. However, within the GD group, CART levels varied significantly according to thyroid ultrasound heterogeneity, with lower levels observed in patients with severe parenchymal heterogeneity. Serum CART levels showed positive correlations with body mass index and insulin resistance indices, while inverse correlations were observed with thyrotropin receptor antibody and anti-thyroid peroxidase antibody levels. No significant associations were identified between serum CART levels and circulating thyroid hormone concentrations. These findings suggest that serum CART may reflect metabolic and autoimmune heterogeneity rather than hypothalamic–pituitary–thyroid axis activity in GD, supporting its role as a context-sensitive, hypothesis-generating biomarker.